. 2018 Mar 24;9(3):877–890. doi: 10.1007/s13300-018-0395-3

Table 2.

Randomized trials of fixed-ratio insulin/glucagon-like peptide-1 receptor agonist combinations

Randomized trials	Study population	HbA1c change from baseline (%)	Patients achieving target HbA1c (< 7.0% (56 mmol/mol) (%)	Change in body weight from baseline (kg)	Hypoglycemia^a	GI adverse events of nausea/vomiting (%)
iGlarLixi studies
LixiLan-O [53]	Insulin-naive; metformin ± 2nd OAD	iGlarLixi: − 1.6 Gla-100: − 1.3 Lixi: − 0.9	iGlarLixi: 74 Gla-100: 59 Lixi: 33	iGlarLixi: − 0.3 Gla-100: + 1.1 Lixi: − 2.3	iGlarLixi: 25.6 Gla-100: 23.6 Lixi: 6.4	iGlarLixi: 1.4 Gla-100: 1.2 Lixi: 0.3	iGlarLixi: 9.6/3.2 Gla-100: 3.6/1.5 Lixi: 24.0/6.4
LixiLan-L [54]	Basal insulin ± ≤ 2 OADs	iGlarLixi: − 1.1 Gla-100: − 0.6	iGlarLixi: 55 Gla-100: 30	iGlarLixi: − 0.7 Gla-100: + 0.7	iGlarLixi: 40.0 Gla-100: 42.5	iGlarLixi: 3.0 Gla-100: 4.2	iGlarLixi:10.4/3.6 Gla-100: 0.5/0.5
IDegLira studies
DUAL-I [50]	Insulin-naive; Metformin ± pioglitazone	IDegLira: − 1.9 IDeg: − 1.4 Lira: − 1.3	IDegLira: 81 IDeg: 65 Lira: 60	IDegLira: − 0.5 IDeg: + 1.6 Lira: − 3.0	IDegLira: 32.0 IDeg: 39.0 Lira: 7.0	IDegLira: 1.8 IDeg: 2.6 Lira: 0.2	IDegLira: 9.0/4.0 IDeg: 4.0/1 Lira: 20.0/8
DUAL-II [52]	Basal insulin + metformin ± other OAD	IDegLira: − 1.9 IDeg: − 0.9	IDegLira: 60 IDeg: 23	IDegLira: − 2.7 IDeg: 0.0	IDegLira: 24.0 IDeg: 25.0	IDegLira: 1.5 IDeg: 2.6	IDegLira: 6.5/nr IDeg: 3.5/nr
DUAL-III [55]	Previous GLP-1 RA + metformin ± other OAD	IDegLira: − 1.3 GLP-1^b: − 0.3	IDegLira: 75 GLP-1^b: 36	IDegLira: + 2.0 GLP-1^b: − 0.8	IDegLira: 32.0 GLP-1^b: 2.8	IDegLira: 2.8 GLP-1^b: 0.1	IDegLira: 3.1/nr GLP-1^b: 4.1/nr
DUAL-IV [56]	Insulin-naive; sulphoylurea ± metformin	IDegLira: − 1.45 Placebo: − 0.46	IDegLira: 79 Placebo: 29	IDegLira: + 0.5 Placebo: − 1.0	IDegLira: 41.7 Placebo: 17.1	IDegLira: 3.5 Placebo: 1.4	IDegLira: 4.5/2.4 Placebo: 3.4/2.7
DUAL-V [51]	Gla-100 + metformin	IDegLira: − 1.8 Gla-100: − 1.1	IDegLira: 72 Gla-100: 47	IDegLira: − 1.4 Gla-100: + 1.8	IDegLira: 28.4 Gla-100: 49.1	IDegLira: 2.2 Gla-100: 5.1	IDegLira: 9.4/nr Gla-100: 1.1/nr

Randomized trials

Study population

HbA1c change from baseline (%)

Patients achieving target HbA1c (< 7.0% (56 mmol/mol) (%)

Change in body weight from baseline (kg)

Hypoglycemia^a

GI adverse events of nausea/vomiting (%)

Patients affected (%)

Events/patient-year

iGlarLixi studies

LixiLan-O [53]

Insulin-naive; metformin ± 2nd OAD

iGlarLixi: − 1.6

Gla-100: − 1.3

Lixi: − 0.9

iGlarLixi: 74

Gla-100: 59

Lixi: 33

iGlarLixi: − 0.3

Gla-100: + 1.1

Lixi: − 2.3

iGlarLixi: 25.6

Gla-100: 23.6

Lixi: 6.4

iGlarLixi: 1.4

Gla-100: 1.2

Lixi: 0.3

iGlarLixi: 9.6/3.2

Gla-100: 3.6/1.5

Lixi: 24.0/6.4

LixiLan-L [54]

Basal insulin ± ≤ 2 OADs

iGlarLixi: − 1.1

Gla-100: − 0.6

iGlarLixi: 55

Gla-100: 30

iGlarLixi: − 0.7

Gla-100: + 0.7

iGlarLixi: 40.0

Gla-100: 42.5

iGlarLixi: 3.0

Gla-100: 4.2

iGlarLixi:10.4/3.6

Gla-100: 0.5/0.5

IDegLira studies

DUAL-I [50]

Insulin-naive;

Metformin ± pioglitazone

IDegLira: − 1.9

IDeg: − 1.4

Lira: − 1.3

IDegLira: 81

IDeg: 65

Lira: 60

IDegLira: − 0.5

IDeg: + 1.6

Lira: − 3.0

IDegLira: 32.0

IDeg: 39.0

Lira: 7.0

IDegLira: 1.8

IDeg: 2.6

Lira: 0.2

IDegLira: 9.0/4.0

IDeg: 4.0/1

Lira: 20.0/8

DUAL-II [52]

Basal insulin + metformin ± other OAD

IDegLira: − 1.9

IDeg: − 0.9

IDegLira: 60

IDeg: 23

IDegLira: − 2.7

IDeg: 0.0

IDegLira: 24.0

IDeg: 25.0

IDegLira: 1.5

IDeg: 2.6

IDegLira: 6.5/nr

IDeg: 3.5/nr

DUAL-III [55]

Previous GLP-1 RA + metformin ± other OAD

IDegLira: − 1.3

GLP-1^b: − 0.3

IDegLira: 75

GLP-1^b: 36

IDegLira: + 2.0

GLP-1^b: − 0.8

IDegLira: 32.0

GLP-1^b: 2.8

IDegLira: 2.8

GLP-1^b: 0.1

IDegLira: 3.1/nr

GLP-1^b: 4.1/nr

DUAL-IV [56]

Insulin-naive; sulphoylurea ± metformin

IDegLira: − 1.45

Placebo: − 0.46

IDegLira: 79

Placebo: 29

IDegLira: + 0.5

Placebo: − 1.0

IDegLira: 41.7

Placebo: 17.1

IDegLira: 3.5

Placebo: 1.4

IDegLira: 4.5/2.4

Placebo: 3.4/2.7

DUAL-V [51]

Gla-100 + metformin

IDegLira: − 1.8

Gla-100: − 1.1

IDegLira: 72

Gla-100: 47

IDegLira: − 1.4

Gla-100: + 1.8

IDegLira: 28.4

Gla-100: 49.1

IDegLira: 2.2

Gla-100: 5.1

IDegLira: 9.4/nr

Gla-100: 1.1/nr

GI Gastrointestinal, Gla-100 insulin glargine 100 U, HbA1c glycated hemoglobin A1c, IDeg insulin degludec, Lira liraglutide, Lixi lixisenatide, nr not reported, OAD oral antidiabetes drug

^aDUAL studies: confirmed or severe hypoglycemia (< 56 mg/dL); LixiLan studies: documented symptomatic hypoglycemia (≤ 70 mg/dL)

^bUnchanged from previous therapy